A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Once a patient has gone through a multitude of treatment regimens, finding a fully suppressive salvage regimen can be impossible. It has long been hypothesized that instead of a complete therapeutic interruption, if the M184V mutation is maintained through drug pressure, this strategy may allow for a slower decline in CD4+ cell count and, as a result, a reduction in clinical disease progression.

To test this hypothesis, Antonella Castagna from Vita-Salute San Raffaele University in Milan et al identified 58 individuals who were experiencing a virologic breakthrough on lamivudine (3TC, Epivir)-containing highly active antiretroviral therapy (HAART). The patients were randomized (29/group) to interrupt therapy (group 1) or to continue lamivudine alone (group 2).

At baseline, patients in groups 1 and 2 were similar with respect to CD4+ cell count (566 versus 580 cells/mm3), HIV plasma viral load (3.7 and 3.8 log10 copies/mL) and years on antiviral therapy/number of agents received (6.9/7 versus 7.0/8).

After 48 weeks, those taking lamivudine experienced a lesser increase in HIV plasma viral load (0.57 versus 1.11 log10 copies/mL) and a lesser decrease in CD4+ cell count (141 versus 215 cells/mm3) than those on a treatment interruption. Failure, i.e., the development of HIV-associated symptoms and/or a decrease in CD4+ cell count to below 350 cells/mm3, was noted in 20/29 (69%) in the treatment interruption group and only 12/29 (41%) in the lamivudine group.

In trial participants who were taking lamivudine, the maintenance of the M184V mutation was associated with a persistent decrease in replicative capacity of the virus isolate, a finding not present in those off all therapy. Once HAART needed to be reinitiated, on either clinical or immunologic grounds (for 15 participants in the treatment interruption group and 10 in the lamivudine group), increases in both CD4+ cell count (196 versus 217 cells/mm3) and virologic suppression (HIV plasma viral load below 50 copies/mL in 6 versus 7 subjects) were identical in both groups.

This is a very courageous study. Virologically, it tells us that lamivudine has residual virologic activity, even in the presence of the M184V mutation. This may be partly mediated by a decrease in the inherent ability of the virus to replicate.

Practically, the data generated from this study offers us an insightful, simple option to discuss with patients who are experiencing a virologic breakthrough and for whom a suppressive regimen cannot be designed. A common situation may be that the drugs we need to give these individuals are still 6-12 months away (when a clinical trial or expanded access program will open), and we are wondering what to do for them. It may be that they are interested in stopping their current regimen. We can now tell them that taking one easily tolerated pill once a day may be better than stopping everything. One caveat is that the patients in this study had near-normal CD4+ cell counts and it is unclear if a similar benefit would apply to patients with more advanced immune disease.

Although it is always better to design a HAART regimen that may lead to maximal virologic suppression, it is also nice to have options like this when this is not possible.

A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information!

Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.

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